tbuckley/cabot-search huggingface dataset:
3D printing of conch-like scaffolds for guiding cell migration and directional bone growth
Authors: Boshi Feng, Meng Zhang, Chen Qin, Dong Zhai, Yufeng Wang, Yanling Zhou, Jiang Chang, Yufang Zhu, Chengtie Wu
Journal: Bioactive Materials (2022)

Regeneration of severe bone defects remains an enormous challenge in clinic. Developing regenerative scaffolds to directionally guide bone growth is a potential strategy to overcome this hurdle. Conch, an interesting creature widely spreading in ocean, has tough spiral shell that can continuously grow along the spiral direction. Herein, inspired by the physiological features of conches, a conch-like (CL) scaffold based on β-TCP bioceramic material was successfully prepared for guiding directional bone growth via digital light processing (DLP)-based 3D printing. Benefiting from the spiral structure, the CL scaffolds significantly improved cell adhesion, proliferation and osteogenic differentiation in vitro compared to the conventional 3D scaffolds. Particularly, the spiral structure in the scaffolds could efficiently induce cells to migrate from the bottom to the top of the scaffolds, which was like "cells climbing stairs". Furthermore, the capability of guiding directional bone growth for the CL scaffolds was demonstrated by a special half-embedded femoral defects model in rabbits. The new bone tissue could consecutively grow into the protruded part of the scaffolds along the spiral cavities. This work provides a promising strategy to construct biomimetic biomaterials for guiding directional bone tissue growth, which offers a new treatment concept for severe bone defects, and even limb regeneration.
Upconverting nanoparticle-containing erythrocyte-sized hemoglobin microgels that generate heat, oxygen and reactive oxygen species for suppressing hypoxic tumors
Authors: Hanju Kim, Johyun Yoon, Hwang Kyung Kim, Woo Tak Lee, Nguyen Thi Nguyen, Xuan Thien Le, Eun-Hee Lee, Eun Seong Lee, Kyung Taek Oh, Han-Gon Choi, Yu Seok Youn
Journal: Bioactive Materials (2022)

Inspired by erythrocytes that contain oxygen-carrying hemoglobin (Hb) and that exhibit photo-driven activity, we introduce homogenous-sized erythrocyte-like Hb microgel (μGel) systems (5-6 μm) that can (i) emit heat, (ii) supply oxygen, and (iii) generate reactive oxygen species (ROS; 1O2) in response to near-infrared (NIR) laser irradiation. Hb μGels consist of Hb, bovine serum albumin (BSA), chlorin e6 (Ce6) and erbium@lutetium upconverting nanoparticles (UCNPs; ∼35 nm) that effectively convert 808 nm NIR light to 660 nm visible light. These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species (1O2) from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity. Moreover, the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme (iron protoporphyrin IX) and display photothermal activity. By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation, it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect. These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.
Economic loss attributable to cigarette smoking in the USA: an economic modelling study
Authors: Nigar Nargis, A K M Ghulam Hussain, Samuel Asare, Zheng Xue, Anuja Majmundar, Priti Bandi, Farhad Islami, K Robin Yabroff, Ahmedin Jemal
Journal: The Lancet Public Health (2022)
Accelerated partner therapy contact tracing for people with chlamydia (LUSTRUM): a crossover cluster-randomised controlled trial
Authors: Claudia S Estcourt, Oliver Stirrup, Andrew Copas, Nicola Low, Fiona Mapp, John Saunders, Catherine H Mercer, Paul Flowers, Tracy Roberts, Alison R Howarth, Melvina Woode Owusu, Merle Symonds, Rak Nandwani, Chidubem Ogwulu, Susannah Brice, Anne M Johnson, Christian L Althaus, Eleanor Williams, Alex Comer-Schwartz, Anna Tostevin, Jackie A Cassell
Journal: The Lancet Public Health (2022)
Third dose of COVID-19 mRNA vaccine appears to overcome vaccine hyporesponsiveness in patients with cirrhosis
Authors: Binu V. John, Raphaella D. Ferreira, Akash Doshi, David E. Kaplan, Tamar H. Taddei, Seth A. Spector, Elizabeth Paulus, Yangyang Deng, Dustin Bastaich, Bassam Dahman
Journal: Journal of Hepatology (2022)
Effectiveness of primary series and booster vaccination against SARS-CoV-2 infection and hospitalisation among adolescents aged 12–17 years in Singapore: a national cohort study
Authors: Calvin J Chiew, M Premikha, Chia Yin Chong, Wycliffe E Wei, Benjamin Ong, David Chien Lye, Derrick Heng, Vernon J Lee, Kelvin Bryan Tan
Journal: The Lancet Infectious Diseases (2022)
Modelling fatty liver disease with mouse liver-derived multicellular spheroids
Authors: Elise Anne van Os, Laura Cools, Nathalie Eysackers, Karolina Szafranska, Ayla Smout, Stefaan Verhulst, Hendrik Reynaert, Peter McCourt, Inge Mannaerts, Leo A. van Grunsven
Journal: Biomaterials (2022)

Chronic liver disease can lead to liver fibrosis and ultimately cirrhosis, which is a significant health burden and a major cause of death worldwide. Reliable in vitro models are lacking and thus mono-cultures of cell lines are still used to study liver disease and evaluate candidate anti-fibrotic drugs. We established functional multicellular liver spheroid (MCLS) cultures using primary mouse hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells and Kupffer cells. Cell-aggregation and spheroid formation was enhanced with 96-well U-bottom plates generating over ±700 spheroids from one mouse. Extensive characterization showed that MCLS cultures contain functional hepatocytes, quiescent stellate cells, fenestrated sinusoidal endothelium and responsive Kupffer cells that can be maintained for 17 days. MCLS cultures display a fibrotic response upon chronic exposure to acetaminophen, and present steatosis and fibrosis when challenged with free fatty acid and lipopolysaccharides, reminiscent of non-alcoholic fatty liver disease (NAFLD) stages. Treatment of MCLS cultures with potential anti-NAFLD drugs such as Elafibranor, Lanifibranor, Pioglitazone and Obeticholic acid shows that all can inhibit steatosis, but only Elafibranor and especially Lanifibranor inhibit fibrosis. Therefore, primary mouse MCLS cultures can be used to model acute and chronic liver disease and are suitable for the assessment of anti-NAFLD drugs.
Radiomics in neuro-oncological clinical trials
Authors: Philipp Lohmann, Enrico Franceschi, Philipp Vollmuth, Frédéric Dhermain, Michael Weller, Matthias Preusser, Marion Smits, Norbert Galldiks
Journal: The Lancet Digital Health (2022)

The development of clinical trials has led to substantial improvements in the prevention and treatment of many diseases, including brain cancer. Advances in medicine, such as improved surgical techniques, the development of new drugs and devices, the use of statistical methods in research, and the development of codes of ethics, have considerably influenced the way clinical trials are conducted today. In addition, methods from the broad field of artificial intelligence, such as radiomics, have the potential to considerably affect clinical trials and clinical practice in the future. Radiomics is a method to extract undiscovered features from routinely acquired imaging data that can neither be captured by means of human perception nor conventional image analysis. In patients with brain cancer, radiomics has shown its potential for the non-invasive identification of prognostic biomarkers, automated response assessment, and differentiation between treatment-related changes from tumour progression. Despite promising results, radiomics is not yet established in routine clinical practice nor in clinical trials. In this Viewpoint, the European Organization for Research and Treatment of Cancer Brain Tumour Group summarises the current status of radiomics, discusses its potential and limitations, envisions its future role in clinical trials in neuro-oncology, and provides guidance on how to address the challenges in radiomics.
Estimating the effect of the wMel release programme on the incidence of dengue and chikungunya in Rio de Janeiro, Brazil: a spatiotemporal modelling study
Authors: Gabriel Ribeiro dos Santos, Betina Durovni, Valeria Saraceni, Thais Irene Souza Riback, Sofia B Pinto, Katherine L Anders, Luciano A Moreira, Henrik Salje
Journal: The Lancet Infectious Diseases (2022)

Introgression of genetic material from species of the insect bacteria Wolbachia into populations of Aedes aegypti mosquitoes has been shown in randomised and non-randomised trials to reduce the incidence of dengue; however, evidence for the real-world effectiveness of large-scale deployments of Wolbachia-infected mosquitoes for arboviral disease control in endemic settings is still scarce. A large Wolbachia (wMel strain) release programme was implemented in 2017 in Rio de Janeiro, Brazil. We aimed to assess the effect of this programme on the incidence of dengue and chikungunya in the city.67 million wMel-infected mosquitoes were released across 28 489 locations over an area of 86·8 km2 in Rio de Janeiro between Aug 29, 2017 and Dec 27, 2019. Following releases, mosquitoes were trapped and the presence of wMel was recorded. In this spatiotemporal modelling study, we assessed the effect of the release programme on the incidence of dengue and chikungunya. We used spatiotemporally explicit mathematical models applied to geocoded dengue cases (N=283 270) from 2010 to 2019 and chikungunya cases (N=57 705) from 2016 to 2019.On average, 32% of mosquitoes collected from the release zones between 1 month and 29 months after the initial release tested positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods in which cases of dengue and chikungunya were historically high, with a decrease to 25% of mosquitoes testing positive for wMel during months in which disease incidence was at its highest. Despite incomplete introgression, we found that the releases were associated with a 38% (95% CI 32-44) reduction in the incidence of dengue and a 10% (4-16) reduction in the incidence of chikungunya.Stable establishment of wMel in the geographically diverse, urban setting of Rio de Janeiro seems to be more complicated than has been observed elsewhere. However, even intermediate levels of wMel seem to reduce the incidence of disease caused by two arboviruses. These findings will help to guide future release programmes.Bill & Melinda Gates Foundation and the European Research Council.
Sustained Minimal Residual Disease Negativity in Multiple Myeloma is Associated with Stool Butyrate and Healthier Plant-Based Diets
Authors: Urvi A. Shah, Kylee H. Maclachlan, Andriy Derkach, Meghan Salcedo, Kelly Barnett, Julia Caple, Jenna Blaslov, Linh Tran, Amanda Ciardiello, Miranda Burge, Tala Shekarkhand, Peter Adintori, Justin Cross, Matthew J. Pianko, Kinga Hosszu, Devin McAvoy, Sham Mailankody, Neha Korde, Malin Hultcrantz, Hani Hassoun, Carlyn R. Tan, Sydney X. Lu, Dhwani Patel, Benjamin Diamond, Gunjan Shah, Michael Scordo, Oscar Lahoud, David J. Chung, Heather Landau, Saad Z. Usmani, Sergio Giralt, Ying Taur, C. Ola Landgren, Gladys Block, Torin Block, Jonathan U. Peled, Marcel R.M. van den Brink, Alexander M. Lesokhin
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Sustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma. The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We hypothesized that dietary factors affect the microbiome (abundance of butyrate-producing bacteria or stool butyrate concentration) and may be associated with multiple myeloma outcomes. Experimental Design: We examined the relationship of dietary factors (via a food frequency questionnaire), stool metabolites (via gas chromatography–mass spectrometry), and the stool microbiome (via 16S sequencing - ±-diversity and relative abundance of butyrate-producing bacteria) with sustained MRD negativity (via flow cytometry at two timepoints 1 year apart) in myeloma patients on lenalidomide maintenance. The Healthy Eating Index 2015 score and flavonoid nutrient values were calculated from the food frequency questionnaire. The Wilcoxon rank sum test was used to evaluate associations with two-sided P &amp;lt; 0.05 considered significant. Results: At 3 months, higher stool butyrate concentration (P = 0.037), butyrate producers (P = 0.025), and ±-diversity (P = 0.0035) were associated with sustained MRD negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (P = 0.009) and sustained MRD negativity (P = 0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins P = 0.01, flavones P = 0.01, and flavanols P = 0.02). Conclusions: This is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production, and sustained MRD negativity in multiple myeloma, providing rationale to evaluate a prospective dietary intervention. Watch the interview with Urvi A. Shah, MD, recipient of the inaugural Clinical Cancer Research Early Career Award: https://vimeo.com/992991936
Lactic acid bacteria and bifidobacteria deliberately introduced into the agro-food chain do not significantly increase the antimicrobial resistance gene pool
Authors: Vita Rozman, Petra Mohar Lorbeg, Primož Treven, Tomaž Accetto, Majda Golob, Irena Zdovc, Bojana Bogovič Matijašić
Journal: Gut Microbes (2022)

Lactic acid bacteria (LAB) and bifidobacteria may serve as reservoirs of antimicrobial resistance, but the risk posed by strains intentionally introduced into the agro-food chain has not yet been thoroughly investigated. The aim of our study was to evaluate whether probiotics, starter and protective cultures, and feed additives represent a risk to human health. In addition to commercial strains of LAB and bifidobacteria, isolates from human milk or colostrum, intestinal mucosa or feces, and fermented products were analyzed. Phenotypic susceptibility data of 474 strains showed that antimicrobial resistance was more common in intestinal isolates than in commercial strains. Antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) were characterized in the whole genome sequences of 1114 strains using comparative genomics. Intrinsic ARGs were abundant in enterococci, bifidobacteria, and lactococci but were considered non-risky due to the absence of MGEs. The results revealed that 13.8% of commercial strains contained acquired ARGs, most frequently for tetracycline. We associated 75.5% of the acquired ARGs with known or novel MGEs, and their potential for transmission was assessed by examining metagenomic sequences. We confirmed that ARGs and MGEs were not as abundant or diverse in commercial strains as in human intestinal isolates or isolates from human milk, suggesting that strains intentionally introduced into the agro-food chain do not pose a significant threat. However, attention should be paid especially to individual probiotic strains containing elements that have been shown to have high potential for transferability in the gut microbiota.Abbreviations: ARG, antimicrobial resistance gene; ICE, integrative and conjugative element; IME, integrative and mobilizable element; LAB, lactic acid bacteria; MDR, multidrug resistance; MIC, minimum inhibitory concentration; MGE, mobile genetic element; TRRPP, tetracycline-resistant ribosomal protection protein; WGS, whole genome sequences
Labour vows to invest in workforce to improve GP access and cut waiting times
Authors: Gareth Iacobucci
Journal: BMJ (2022)

Eszopiclone (Lunesta; Sepracor, Marlborough, MA) and zolpidem [<i>N</i>,<i>N</i>,6-trimethyl-2-(4-methylphenyl)-imidazo(1,2-<i>a</i>)pyridine-3-acetamide] are among the most commonly prescribed hypnotics in use in the United States. The thalamus plays a pivotal role in sleep regulation and rhythmicity. Two distinct subtypes of synaptic GABA<sub>A</sub> receptors (GABA<sub>A</sub>-Rs), α<sub>1</sub>β<sub>2</sub>γ<sub>2</sub> and α<sub>3</sub>β<sub>3</sub>γ<sub>2</sub>, are expressed in thalamocortical relay neurons and in interneurons of the RTN (reticular thalamic nucleus), respectively. Thalamocortical neurons also express extrasynaptic GABA<sub>A</sub>-Rs composed of α<sub>4</sub>β<sub>2</sub>δ subunits. In this study, we compared the effects of eszopiclone and zolpidem on miniature inhibitory postsynaptic currents (IPSCs), spontaneous IPSCs, and tonic inhibition in the mouse thalamus. Eszopiclone (0.1-1 μM) slowed the decay phase of IPSCs recorded from RTN neurons, whereas zolpidem was less effective and increased the decay time constant only at ≥0.3 μM. IPSCs of RTN neurons were more sensitive to eszopiclone than zolpidem at all concentrations tested. On the other hand, IPSCs of relay neurons in the ventrobasal nucleus (VB) were more sensitive to zolpidem than eszopiclone. Zolpidem (0.1-1 μM) prolonged the decay of IPSCs from VB neurons, whereas eszopiclone increased the decay time constant only at ≥0.3 μM. Neither of these two hypnotics affected tonic inhibition in relay neurons. Our results demonstrate that eszopiclone has greater efficacy at synaptic GABA<sub>A</sub>-Rs of RTN neurons than in relay neurons, whereas zolpidem exerts bigger effects on relay neurons than RTN neurons. This distinct pattern of activity on thalamic neurons may contribute to some of the observed differences in the clinical effects of these two hypnotics.
Early-Life Exposure to PM<sub>2.5</sub> and Sleep Disturbances in Preschoolers from 551 Cities of China
Authors: Jing Cai, Yang Shen, Yan Zhao, Xia Meng, Yue Niu, Renjie Chen, Guangbin Quan, Huichu Li, John A. Groeger, Wenchong Du, Jing Hua, Haidong Kan
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Air pollution has been linked with sleep disturbance in adults, but the association in children remains unclear. Objectives: To examine the associations of prenatal and postnatal exposure to fine particulate matter (particulate matter ⩽2.5 μm in aerodynamic diameter; PM2.5) with sleep quality and sleep disturbances among children in 551 Chinese cities. Methods: A total of 1,15,023 children aged 3–7 years from the Chinese National Cohort of Motor Development were included. Sleep quality was measured using the Children’s Sleep Habits Questionnaire (CSHQ). PM2.5 exposure was estimated using a satellite-based model. Generalized additive mixed models with Gaussian and binomial distributions were used to examine the associations of PM2.5 exposure with CSHQ scores and risk of sleep disturbance, respectively, adjusting for demographic characteristics and temporal trends. Measurements and Main Results: Early-life PM2.5 exposure was associated with higher total CSHQ score, and the association was stronger for exposure at age 0–3 years (change of CSHQ score per interquartile range increase of PM2.5 = 0.46; 95% confidence interval [CI], 0.29–0.63) than during pregnancy (0.22; 95% CI, 0.12–0.32). The associations were more evident in sleep-disordered breathing and daytime sleepiness. Postnatal PM2.5 exposure was associated with increased risk of sleep disturbance (adjusted odds ratio for per–interquartile range increase of PM2.5 exposure at age 0–3 years, 1.10; 95% CI, 1.04–1.15), but no associations were found for prenatal exposure. Children who were exclusively breastfed for <6 months and had neonatal ICU admission may be more vulnerable to sleep disturbance related to PM2.5 exposure. Conclusions: PM2.5 exposure can impair sleep quality in preschool children.
Antiviral Responses of Tissue-resident CD49a<sup>+</sup> Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease
Authors: Grace E. Cooper, Jemma Mayall, Chantal Donovan, Tatt J. Haw, Kurtis F. Budden, Nicole G. Hansbro, Evy E. Blomme, Tania Maes, Chia Wei Kong, Jay C. Horvat, Salim I. Khakoo, Tom M. A. Wilkinson, Philip M. Hansbro, Karl J. Staples
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Tissue-resident natural killer (trNK) cells have been identified in numerous organs, but little is known about their functional contribution to respiratory immunity, in particular during chronic lung diseases such as chronic obstructive pulmonary disease (COPD). Objectives: To investigate the phenotype and antiviral responses of trNK cells in murine cigarette smoke–induced experimental COPD and in human lung parenchyma from COPD donors. Methods: Mice were exposed to cigarette smoke for 12 weeks to induce COPD-like lung disease. Lung trNK cell phenotypes and function were analyzed by flow cytometry in both murine and human disease with and without challenge with influenza A virus. Measurements and Main Results: In the mouse lung, CD49a+CD49b+EOMES+ and CD49a+CD49b−EOMESlo NK cell populations had a distinct phenotype compared with CD49a− circulating NK cells. CD49a+ NK cells were more extensively altered earlier in disease onset than circulating NK cells, and increased proportions of CD49a+ NK cells correlated with worsening disease in both murine and human COPD. Furthermore, the presence of lung disease delayed both circulating and trNK cell functional responses to influenza infection. CD49a+ NK cells markedly increased their NKG2D, CD103, and CD69 expression in experimental COPD after influenza infection, and human CD49a+ NK cells were hyperactive to ex vivo influenza infection in COPD donors. Conclusions: Collectively, these results demonstrate that trNK cell function is altered in cigarette smoke–induced disease and suggests that smoke exposure may aberrantly prime trNK cell responsiveness to viral infection. This may contribute to excess inflammation during viral exacerbations of COPD.
Remodeling Phenotypes Take Center Stage in the Prediction of Preschool Wheeze Attacks
Authors: Sejal Saglani, Simonetta Baraldo
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Remodelling Phenotypes Take Centre Stage in the Prediction of Preschool Wheeze Attacks." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Frontline Therapy in Mantle Cell Lymphoma: When Clinical Trial and Real-World Data Collide
Authors: Timothy S. Fenske
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. A large number of frontline treatment options exist for mantle cell lymphoma (MCL), making selection of therapy a challenge for the clinician. In this Oncology Grand Rounds article, the case of a 73-year-old woman with MCL who attained remission with bendamustine and rituximab is presented. The relevant literature regarding frontline therapy is then reviewed, with particular focus on selection of induction regimen and the potential roles for autologous transplantation and/or rituximab maintenance. This literature primarily consists of prospective phase 2 and phase 3 clinical trials; however, added to this literature now is a growing body of large retrospective real-world cohorts, such as the new analysis by Martin et al, 35 the manuscript that accompanies this Oncology Grand Rounds article. In some cases, the real-world evidence is at odds with data from prospective clinical trials, such as regarding the role of rituximab maintenance after bendamustine plus rituximab induction. These important new real-world data are put into context of an ever-changing treatment landscape, in hopes of aiding clinicians in frontline treatment selection for patients with MCL.